2 50 BIOLOGY OF THE LABORATORY MOUSE 



In the meantime Wright (105, 106), who had started the genetic analysis 

 of a large number of strains of closely inbred guinea-pigs at the U.S. Depart- 

 ment of Agriculture, began to publish results which showed, (i) that the 

 incidence of certain morphological genetic abnormalities could differ in 

 different inbred lines, and (2) that non-genetic factors often influenced the 

 incidence of such characters, within a strain, more than did genes. The 

 foundation for a much more complex interpretation of the bio-genetics of 

 tumor formation was thus laid by evidence of a far from simple situation in 

 the genetics of other growth abnormalities. 



The history of the development of our knowledge concerning the genetics 

 of spontaneous tumor formation in mice has followed the trend of recognizing 

 more and more complicating factors. 



Slye's original theory (1913-1937) that all types of cancer in mice were 

 due to a single recessive Mendelian gene has been replaced by evidence that 

 there is a high degree of specificity as regards type and location of neoplastic 

 change. Various physiological factors such as age, sex and coat color have 

 some influence on the expression of the genetic constitution and its relation 

 to tumor formation. 



Lynch (61) gave evidence suggestive of the possible partial dominance of 

 the tendency to form breast tumors. Little (52) showed that Slye's data 

 were not incompatible to some such interpretation. The discovery of an 

 extra-chromosomal maternal influence on the incidence of breast tumors in 

 mice was announced by the staft" of the Roscoe B. Jackson Memorial 

 Laboratory (44) and independently by Korteweg (46). This was further 

 investigated by Murray and Little (77). Bittner (15) made an important 

 discovery that an extra-chromosomal influence affecting breast tumor 

 incidence could be transmitted from parent to offspring apparently through 

 the milk. 



In the meantime data were being gathered to show that lung tumors 

 (chiefly adenocarcinomas) and non-epithelial tumors, chiefly lymphosar- 

 comas, fibrosarcomas and endotheliomas, were two other categories of neo- 

 plasms quite largely distinct from mammary carcinomas and from one 

 another. A fourth group, strictly speaking a subdivision within the non- 

 epithelial tumor class, may well be made to include at least certain of the 

 leukemias. The excellent work of MacDowell, Richter and others (67-70) 

 supports such a subdivision. All of these steps were clear indicators of an 

 increasing complexity in the inherent nature of the genetic process. 



We may very briefly review the more important data which have led to 

 the creation of at least four distinct biological groups of spontaneous tumors 

 in mice. 



